LPS-induced PI3K-δ signaling activation damages the ultrastructure of respiratory epithelium = LPS-induced PI3K-δ signaling activation damages the ultrastructure of respiratory epithelium

다국어 초록 (Multilingual Abstract)

To date, the knowledge of the role of phosphatidylinositol-3-kinase (PI3K)-δ, one of the members of PI3K class I has focused its action on immune/inflammatory cells and stimulation of various cellular signalings. In this study, we aimed to evaluate the changes of the ultrastructure of respiratory epithelium with cilia arrangement in LPS-induced lung injury using scanning electron microscope (SEM) and to define the role of PI3K-δ signaling activation in the changes of structure of respiratory epithelium. Our results showed that LPS-instilled mice showed typical features of acute lung injury; pulmonary neutrophilia, vascular leakage, and nuclear translocation of nuclear factor-κB (NF-κB) and PI3K-δ activation. We also found that the p110δ catalytic subunit and p85 regulatory subunit were increased in LPS-stimulated epithelial cells. Interestingly, SEM images revealed that the respiratory epithelium was damaged severely after LPS instillation exhibiting decreased numbers of epithelial cells, loss of cilia, the disarrangement of epithelial lining, and the massive amount of thick mucus layer with the irregular surface. The treatment with PI3K-δ inhibitor, IC87114 restored the damaged structure of respiratory epithelium with cilia and decreased the mucus and exudation on SEM images. Besides, IC87114 substantially improved the LPS-induced lung injury compared to the mice treated with vehicle only. These findings suggest that PI3K- δ signaling activation can be a pathogenic contributor to LPS-induced lung injury partly through the destruction of respiratory epithelium.